Tissue Damage In Organs Research Articles

Therapeutic Potential of Insect Defensin DLP4 Against Staphylococcus hyicus-Infected Piglet Exudative Epidermitis.

Background/Objectives: The emergence of resistance to Staphylococcus hyicus (S. hyicus), the major cause of exudative epidermatitis (EE) in piglets, has led to the need for new antimicrobial agents. The study aimed to evaluate the potential efficacy of the insect defensin DLP4 against EE in piglets caused by clinically isolated S. hyicus ACCC 61734. Methods and Results: DLP4 showed strong antibacterial activity against S. hyicus ACCC 61734 (minimum inhibitory concentration, MIC: 0.92 μM, median effect concentration, EC50: 3.158 μM). DLP4 could effectively inhibit the formation of S. hyicus early biofilm with an inhibition rate of 95.10-98.34% and eradicate mature biofilm with a clearance rate of 82.09-86.41%, which was significantly superior to that of ceftriaxone sodium (CRO). Meanwhile, DLP4 could efficiently inhibit bacteria in early and mature biofilm, killing up to 95.3% of bacteria in early biofilm and 87.2-90.3% of bacteria in mature biofilm. The results showed that DLP4 could be effective in alleviating the clinical symptoms of EE by down-regulating the nuclear factor κB (NF-κB) signaling pathway, balancing cytokines, inhibiting bacterial proliferation, and reducing organ tissue damage. Conclusions: This study firstly demonstrated the potential efficacy of DLP4 against EE caused by S. hyicus ACCC 61734 infection in piglets, which may be used as an alternative to antibiotics in treating EE.

Sirtuins and mechanisms of diabetic lung damage: a scientific discussion. A review

Induced tissue damage in target organs (kidneys, heart, eyes, liver, skin, nervous system) significantly contributes to the morbidity and mortality of patients from diabetes mellitus (DM). In recent decades, the question has been actively discussed: should the lungs be regarded as a target organ for diabetes? The c collected data demonstrate histological and functional lung disorders in DM patients. This suggests that the lungs are a target organ for diabetes. It is known that sirtuins regulate a number of physiological processes and affect obesity, insulin resistance, type 2 DM, heart disease and aging. In this review, we have tried to summarize the knowledge about the contribution of sirtuins to cellular regulation and the formation of pulmonary disease in patients with type 2 DM.

Silver nanoparticles exhibit ecotoxicological effects via oxidative stress, inflammation, and reproductive toxicity in Asian clam (Corbicula fluminea)

Silver nanoparticles (AgNPs) are pervasive environmental pollutants capable of inducing toxicological impacts on benthic organisms. In this study, the effects of AgNPs on the antioxidant enzyme activities, tissue damage, inflammatory responses, and reproductive toxicity of Corbicula fluminea were investigated. C. fluminea was exposed to four concentrations of AgNPs (0, 5 mg/L, 10 mg/L, and 125 mg/L) for 48 h. The results showed that the higher concentrations of AgNPs caused severe tissue damage in multiple organs of C. fluminea, induced oxidative stress and an imbalance of the antioxidant enzyme activities (such as SOD, CAT, MDA), and increased the inflammatory immune response involving NFκB, TLR2/4, HSP70/90, IL1β, and TNFα. Notably, further transmission electron microscopy and cytological analyses revealed that AgNPs exposure induced apoptosis in the gonad tissues, resulting in significant loss and damage in the oocytes and spermatids. The present study demonstrates the ecotoxicological impacts of AgNPs on freshwater bivalves, particularly highlighting their reproductive toxicity on germ cells, signifying the potential toxic effects of heavy metal pollution on aquatic ecosystems.

Pathogenicity of duck circovirus and novel goose parvovirus co-infection in SPF ducks

ABSTRACT Duck circovirus (DuCV) is one of the most prevalent infectious viruses in the duck industry in China. Although the clinical signs vary, it often causes immunosuppression in the host and leads to secondary infection with other pathogens. Novel goose parvovirus (NGPV) mainly infects ducks and causes short beak and dwarfism syndrome in ducks. However, the incidence of infection in ducks has increased in recent years, and the phenomenon of mixed infection with DuCV is common, resulting in more severe clinical morbidity. However, there are no systematic studies evaluating the presence of mixed infections. In order to investigate the synergistic pathogenicity of DuCV and NGPV co-infection in SPF ducks, a comparative experiment using DuCV and NGPV co-infection and mono-infection bird models was established. The results showed that the clinical signs of short beak, dwarfism and immunosuppression were more obvious in DuCV and NGPV co-infected ducks; the tissue damage of target organs was more serious, and the viral titre in organs and cloacal swabs were more significant compared with those of SPF ducks infected with only one virus. The results indicated that co-infection with DuCV and NGPV could promote viral replication and cause more severe tissue damage and immunosuppression than single virus infection. The present study reveals that the co-infection of NGPV and DuCV has a synergistic pathogenic effect from the aspect of pathogenicity, and the conclusions drawn not only clarify the direction of the subsequent research on the mechanism of co-infection of NGPV and DuCV, but also provide a scientific basis for the research on the co-infection of immunosuppressive pathogens and other pathogens.

Immune checkpoint inhibitor therapy‑related pneumonitis: How, when and why to diagnose and manage (Review).

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by enhancing the immune response against tumor cells. However, their influence on immune pathways can lead to immune-related adverse events such as pneumonitis, necessitating rapid diagnosis and management to prevent severe complications. These adverse events arise from the activation of the immune system by immunotherapeutic drugs, leading to immune-mediated inflammation and tissue damage in various organs and tissues throughout the body. The present review article discusses the pathophysiology, clinical presentation, diagnostic modalities and management strategies for ICI-related pneumonitis, emphasizing early recognition and tailored interventions. Future research endeavors should focus on elucidating the underlying mechanisms of pneumonitis and identifying predictive biomarkers to guide personalized treatment strategies in this evolving field of oncology.

Protective effect of freeze-dried extract of Persicaria bistorta Samp. on acetic acid-induced colitis model in rats: Involvement of nitric oxide and opioid system.

Inflammatory bowel disease is a chronic inflammatory disorder accompanied by occasional flare-ups, abdominal pain, and rectal bleeding.Persicaria bistorta Samp. is a medicinal plant repeatedly mentioned in traditional Persian medicine for the treatment of bleeding and tissue damage in different organs, including the intestines. The current study aimed to evaluate the effect of bistort root in an animal model of colitis. Freeze-dried aqueous extract of the plant (PB) was prepared and analyzed using liquid chromatography-mass spectrometry and high-performance liquid chromatography. The anti-inflammatory effect of oral PB (300, 500, and 700mg/kg) was evaluated in acetic acid-induced colitis in Wistar rats compared with negative control and positive control (dexamethasone). The role of nitric oxide (NO), opioid receptors, Toll-like receptors (TLR-4), interleukin (IL)-1β, IL-6, TNF-α, NF-κB, myeloperoxidase, and intestinal tissue damage using immunohistochemistry staining for cyclooxygenase-2 (COX-2) were also assessed. A total of 29 compounds were identified in the extract. The gallic acid content of the extractwas 4.973 ± 1.102mg/g. PB significantly ameliorated the gross morphological damage from 4.66 ± 0.577 in negative control to 1.33 ± 0.56 in PB 700 (p < 0.001). Also, PB 700 lowered the levels of TNF-α (p < 0.01), TLR-4 (p < 0.001), NF-κB (p < 0.0001), IL-1β (p < 0.0001), and IL-6 (p < 0.0001) compared to the negative control. Additionally, while blocking NO and opioid pathways, the therapeutic effect of the extract was not significant, compared to the negative control, suggesting that PB 700 has exerted its therapeutic effect via these two pathways. However, further mechanistic and clinical studies are recommended to confirm PB as a natural treatment for colitis.

Protective Effects of the Aqueous Extract of Malva sylvestris Plant against the Lethality and Histopathological Damage in Experimental Envenoming of Hemiscorpius lepturus Venom in Balb/c Mice.

Hemiscorpius lepturus envenomation is a serious health problem in the southern provinces of Iran. The antiserum produced in Iran to counteract this scorpion venom is not entirely effective due to the risk of anaphylactic shock and other adverse effects. Therefore, more efficient alternatives to treat patients deserve attention, and plants are extensively good candidates to be studied. This study aimed to assess the potential of the aqueous fraction of Malva sylvestris in inhibiting the toxic effects of H. lepturus venom. Injection of sub-lethal dose of H. lepturus venom leads to severe tissue damage in vital organs including the kidney, liver, heart and intestine, after 24 hours. By injecting 80 mg of the aqueous extract of M. sylvestris into the peritoneum helped treat the damaged tissues caused by H. lepturus venom in mice. Thus, Malva sylvestris could serve as an alternative treatment for scorpion sting envenomation and may be used as a drug to neutralize relevant toxic effects in patients stung by H. lepturus.

Behavioral, biochemical and histopathological alterations induced in Swiss mice by Buthus boumalenii scorpion venom

The yellow scorpion, Buthus boumalenii, has long been recognized as a potentially dangerous species endemic to Morocco. However, there is currently no data on the in vivo toxicity or effects of Buthus boumalenii venom, as it has not been studied to the best of our knowledge. In order to achieve the objective of this study, the LD50 of B. boumalenii venom will be initially calculated, followed by determining its impact on vital organs using histological, biochemical, and behavioral analyses. The investigation also explores potential neurobehavioral impairments in Swiss mice at intervals of 3 hours, 6 hours, and 12 hours post-envenomation. The LD50 for Buthus boumalenii scorpion venom in mice was determined to be 353 µg/kg based on body weight. The findings of the study highlight the potential lethality of B. boumalenii. Observations related to the poisoning provide indications of potential tissue damage in specific vital organs. To sum up, the venom from this scorpion has the potential to result in considerable medical complications, including fatalities, particularly in individuals at risk. Consequently, healthcare practitioners should be knowledgeable about the diverse scorpion species in their regions and adhere to contemporary medical protocols when addressing scorpion envenomation.

The feasibility of K XRF bone lead measurements in mice assessed using 3D-printed phantoms

This article describes the development of a system for in vivo measurements of lead body burden in mice using 109Cd K x-ray fluorescence (XRF). This K XRF system could facilitate early-stage studies on interventions that ameliorate or reverse organ tissue damage from lead poisoning by reducing animal numbers through a cross-sectional study approach. A novel mouse phantom was developed based on a mouse atlas and 3D-printed using PLA plastic with plaster of Paris ’bone’ inserts. PLA plastic was found to be a good surrogate for soft tissue in XRF measurements and the phantoms were found to be good models of mice. As expected, lead detection limits varied with mouse size, mouse orientation, and mouse position with respect to the source and detector. The work suggests that detection limits of 10 to 20 μg Pb per g bone mineral may be possible for a 2 to 3 hour XRF measurement in a single animal, an adequate limit for some pre-clinical studies. The 109Cd K XRF mouse measurement system was also modeled using the Monte Carlo code MCNP. The combination of experiment and modeling found that contrary to expectation, accurate measurements of lead levels in mice required calibration using mouse-specific calibration standards due to the coherent scatter peak normalization failing when small animals are measured. MCNP modeling determined that this was because the coherent scatter signal from soft tissue, which until now has been assumed negligible, becomes significant when compared to the coherent scatter signal in bone in small animals. This may have implications for some human measurements. This work suggests that 109Cd K x-ray fluorescence measurements of lead body burden are precise enough to make the system feasible for small animals if appropriately calibrated. Further work to validate the technology’s measurement accuracy and performance in vivo will be required.

Investigation Few Biomarkers for Pantoea Infection with Systemic Lupus Erythematosus Patients

Background: Systemic lupus erythematosus (SLE) is a disease known as systemic lupus erythematosus. SLE is an autoimmune condition in which the immune system attacks the body’s own tissues, leading to extensive tissue damage and inflammation in other organs. One of the most frequent causes of death and morbidity in SLE patients is infection. Patients with SLE may contract a genus of gram-negative bacteria called Pantoea. This study aims to find biomarkers for Pantoea infection in SLE patients in Iraq’s Najaf Governorate. Methods: About 60 individuals with systemic lupus erythematosus from Al-Sader Medical City in Al-Najaf Province had blood samples taken at a specialized rheumatology and nephrology center between September 2022 and February 2023. Some bio-markers has been evaluated. Results: The results of microbiological analyses indicate that 26/60 samples contain bacteria. Pantoea was discovered in 3 (11.6%) of the 26 specimens. Despite SLE, increased autoantibody levels in patients. The results of this analysis indicate a significant decrease in Hb, WBC, and platelet levels. In contrast to the control group, the serum levels of CD69, IL-21, and IL-35 increased significantly. Conclusion: Pantoea produces elevated diagnostic and immunological parameters in SLE patients. Consequently, it is necessary to conduct assays to identify bacterial infections in patients, with a significant increase in CD69, IL-21, and IL-35 in the event that SLE patients are infected with bacteria.

Association between lung contusion volume and acute changes in fibrinogen levels: A single-center observational study.

Organ tissue damage, including the lungs, may lead to acute coagulopathy. This study aimed to evaluate the association between lung contusion volume and serum fibrinogen level during the acute phase of trauma. We conducted an observational study using electronic medical records at a tertiary-care center between January 2015 and December 2018. We included patients with lung contusions on hospital arrival. We used three-dimensional computed tomography to calculate lung contusion volumes. The primary outcome was the lowest fibrinogen level measured within 24 h of hospital arrival. We evaluated the association between lung contusion volume and outcome with multivariable linear regression analysis. Also, we calculated the sensitivity and specificity of lung contusion volume in patients with a serum fibrinogen level of ≤150 mg/dL. We identified 124 eligible patients. Their median age was 43.5 years, and 101 were male (81.5%). The median lung contusion volume was 10.9%. The median lowest fibrinogen level within 24 h from arrival was 188.0 mg/dL. After adjustment, lung contusion volume had a statistically significant association with the lowest fibrinogen level within 24 h from arrival (coefficient -1.6, 95% confidence interval -3.16 to -0.07). When a lung contusion volume of 20% was used as the cutoff, the sensitivity and specificity to identify fibrinogen depletion were 0.27 and 0.95, respectively. Lung contusion volume was associated with the lowest fibrinogen level measured within 24 h from hospital arrival. Measuring lung contusion volume may help to identify patients with a progression of fibrinogen depletion.

Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction.

Tissue damage and functional abnormalities in organs have become a considerable clinical challenge. Organoids are often applied as disease models and in drug discovery and screening. Indeed, several studies have shown that organoids are an important strategy for achieving tissue repair and biofunction reconstruction. In contrast to established stem cell therapies, organoids have high clinical relevance. However, conventional approaches have limited the application of organoids in clinical regenerative medicine. Engineered organoids might have the capacity to overcome these challenges. Bioengineering-a multidisciplinary field that applies engineering principles to biomedicine-has bridged the gap between engineering and medicine to promote human health. More specifically, bioengineering principles have been applied to organoids to accelerate their clinical translation. In this review, beginning with the basic concepts of organoids, we describe strategies for cultivating engineered organoids and discuss the multiple engineering modes to create conditions for breakthroughs in organoid research. Subsequently, studies on the application of engineered organoids in biofunction reconstruction and tissue repair are presented. Finally, we highlight the limitations and challenges hindering the utilization of engineered organoids in clinical applications. Future research will focus on cultivating engineered organoids using advanced bioengineering tools for personalized tissue repair and biofunction reconstruction.

The role of insulin signaling with FOXO and FOXK transcription factors.

Insulin is an essential hormone for animal activity and survival, and it controls the metabolic functions of the entire body. Throughout the evolution of metazoan animals and the development of their brains, a sustainable energy supply has been essential to overcoming the competition for survival under various environmental stresses. Managing energy for metabolism, preservation, and consumption inevitably involves high oxidative stress, causing tissue damage in various organs. In both mice and humans, excessive dietary intake can lead to insulin resistance in various organs, ultimately displaying metabolic syndrome and type 2 diabetes. Insulin signals require thorough regulation to maintain metabolism across diverse environments. Recent studies demonstrated that two types of forkhead-box family transcription factors, FOXOs and FOXKs, are related to the switching of insulin signals during fasting and feeding states. Insulin signaling plays a role in supporting higher activity during periods of sufficient food supply and in promoting survival during times of insufficient food supply. The insulin receptor depends on the tyrosine phosphatase feedback of insulin signaling to maintain adipocyte insulin responsiveness. α4, a regulatory subunit of protein phosphatase 2A (PP2A), has been shown to play a crucial role in modulating insulin signaling pathways by regulating the phosphorylation status of key proteins involved in these pathways. This short review summarizes the current understanding of the molecular mechanism related to the regulation of insulin signals.

Hipnokomunikasi Dalam Aplikasi Pasha (Pain Assessment, Stimulating And Healing Application) Dalam Menurunkan Nyeri Pasien Post Operasi

Postoperative pain is the body’s reaction to tissue damage (ranging from skin incisions to damage from surgery), stretching or tightening of internal organs, and diseases (eg cancer, spinal diseases, etc). There are several pain management options in the PASHA (Pain Assessment, Stimulating and Healing Application) application to reduce the pain scale felt by patients, one of which is hypnocommunication. The purpose of this study was to find out how effective hypnocommunication on reducing pain of postoperative patients. This study used a quasy experimental design with a one-group pre-test and post-test approach by measuring the pain scale using the NRS (Numeric Rating Scales). The sample of this study was 30 postoperative patients in the surgical room who were selected by purposive sampling with several inclusion criteria.. The intervention was carried out using the PASHA application and the patient was listened hypnocommunication therapy for 15 minutes in 2 consecutive days The data were collected through computerization by using an dependent t-test. The results of the study showed that the average respondent’s pain intensity before being given hypnocommunication was 5.167 (moderate pain) and the average repondent’s pain intensity after being given hypnocommunication was 4, 00 (moderate pain). It can be conclude there was a significant effect of providing hypnocommunication based on the PASHA application in reducing postoperative patient pain (p value = 0.001). It is recommended to nurses especially in treating pain of postoperative patients by applying hypnocommunication as a non pharmacological pain therapy

Protection effects of mice liver and lung injury induced by coronavirus infection of Qingfei Paidu decoction involve inhibition of the NLRP3 signaling pathway

Ethnopharmacological relevanceCoronavirus Disease 2019 (COVID-19) is a grave and pervasive global infectious malady brought about by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), posing a significant menace to human well-being. Qingfei Paidu decoction (QFPD) represents a pioneering formulation derived from four classical Chinese medicine prescriptions. Substantiated evidence attests to its efficacy in alleviating clinical manifestations, mitigating the incidence of severe and critical conditions, and reducing mortality rates among COVID-19 patients. Aim of the studyThis study aims to investigate the protection effects of QFPD in mice afflicted with a coronavirus infection, with a particular focus on determining whether its mechanism involves the NLRP3 signaling pathway. Materials and methodsThe coronavirus mice model was established through intranasal infection of Kunming mice with Hepatic Mouse Virus A59 (MHV-A59). In the dose-effect experiment, normal saline, ribavirin (80 mg/kg), or QFPD (5, 10, 20 g/kg) were administered to the mice 2 h following MHV-A59 infection. In the time-effect experiment, normal saline or QFPD (20 g/kg) was administered to mice 2 h post MHV-A59 infection. Following the assessment of mouse body weights, food consumption, and water intake, intragastric administration was conducted once daily at consistent intervals over a span of 5 days. The impact of QFPD on pathological alterations in the livers and lungs of MHV-A59-infected mice was evaluated through H&E staining. The viral loads of MHV-A59 in both the liver and lung were determined using qPCR. The expression levels of genes and proteins related to the NLRP3 pathway in the liver and lung were assessed through qPCR, Western Blot analysis, and immunofluorescence. ResultsThe administration of QFPD was shown to ameliorate the reduced weight gain, decline in food consumption, and diminished water intake, all of which were repercussions of MHV-A59 infection in mice. QFPD treatment exhibited notable efficacy in safeguarding tissue integrity. The extent of hepatic and pulmonary injury, when coupled with QFPD treatment, demonstrated not only a reduction with higher treatment dosages but also a decline with prolonged treatment duration. In the dose-effect experiment, there was a notable, dose-dependent reduction in the viral loads, as well as the expression levels of IL-1β, NLRP3, ASC, Caspase 1, Caspase-1 p20, GSDMD, GSDMD-N, and NF-κB within the liver of the QFPD-treated groups. Additionally, in the time-effects experiments, the viral loads and the expression levels of genes and proteins linked to the NLRP3 pathway were consistently lower in the QFPD-treated groups compared with the model control groups, particularly during the periods when their expressions reached their zenith in the model group. Notably, IL-18 showed only a modest elevation relative to the blank control group following QFPD treatment. ConclusionsTo sum up, our current study demonstrated that QFPD treatment has the capacity to alleviate infection-related symptoms, mitigate tissue damage in infected organs, and suppress viral replication in coronavirus-infected mice. The protective attributes of QFPD in coronavirus-infected mice are plausibly associated with its modulation of the NLRP3 signaling pathway. We further infer that QFPD holds substantial promise in the context of coronavirus infection therapy.

Research Progress in Stress-Induced Senescence of Renal Tubular Cells in Diabetic Nephropathy

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Renal tubulointerstitial injury is an important pathophysiological basis that contributes to the progression of DN to end-stage renal disease. Stress-induced senescence of renal tubular epithelial cells (RTECs) forms a key link that causes tubulointerstitial injury. In recent years, it has been reported that organelles, such as endoplasmic reticulum, mitochondria, and lysosomes, in RTECs are damaged to varying degrees in DN, and that their functional imbalance may lead to stress-induced senescence of RTECs, thereby causing sustained cellular and tissue-organ damage, which in turn promotes the progression of the disease. However, the core mechanism underlying changes in the senescence microenvironment caused by stress-induced senescence of RTECs in DN is still not understood. In addition, the mechanism by which organelles lose homeostasis also needs to be further investigated. Herein, we described the specific pathophysiological mechanisms of renal tubular injury, stress-induced senescence of RTECs, and their association with organelles in the context of DN in order to provide reference for the next-step research, as well as the development of new therapeutic strategies.

Studies on the Effects of Hypercholesterolemia on Mouse Ophthalmic Artery Reactivity.

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, the vascular mechanics, lipid content, levels of reactive oxygen species (ROS), and expression of pro-oxidant redox enzymes and the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, the levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via the involvement of LOX-1, NOX1, and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. A lack of LOX-1 expression/overexpression in response to increased oxidized low-density lipoprotein levels may be a possible mechanism of action.

ET-traps: Potential therapeutics for preeclampsia

Elevated endothelin-1 (ET-1) has been implicated in several diseases including preeclampsia, where it causes the induction of hypertension, oxidative stress, endoplasmic reticulum stress, microvascular dysfunction and tissue damage in different organs. ET-traps are Fc-fusion proteins with a design based on the physiological receptors of ET-1. This paper discusses the potential use of ET-traps as a therapeutic for preeclampsia. ET-traps potently bind and sequester pathologically elevated ET-1 to significantly reduce different markers of pathology to non-disease levels with no toxicity.

Global LC-MS/MS targeted metabolomics using a combination of HILIC and RP LC separation modes on an organic monolithic column based on 1-vinyl-1,2,4-triazole

The paper presents an LC-MS/MS-based approach to targeted screening of both polar and non-polar metabolites using a synthesized monolithic column which is a copolymer of styrene, divinylbenzene, and 1-vinyl-1,2,4-triazole. It was shown that this column in combination with eluents 20 mM (NH4)2CO3 + NH3 (pH = 9.8, eluent A) and ACN (eluent B) allows for separation of metabolites of different nature in two modes, HILIC and RP LC, and these methods are mutually complementary. A combination of analyses based on these two modes was proposed, allowing detection of about 400 metabolites in a total time of less than 30 min. Comparison of the developed method with those utilizing commercially available columns with sorbents of various types showed that it could provide a broader metabolite coverage. Using the developed approach, metabolomic screening of dried blood spots samples of mice exposed with X-ray was performed, and metabolites that could be considered as possible markers of irradiation exposure and organ tissue damage were detected. Analysis of marker metabolites revealed metabolic pathways that were altered by radiation exposure. Comparison of the results with literature data showed the effectiveness of the developed metabolomic screening approach.

Potential of a bivalent vaccine for broad protection against enterovirus 71 and coxsackie virus 16 infections causing hand, foot, and mouth disease

Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection that is mainly caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16). As there are no specific therapeutics for HFMD, the development of a bivalent vaccine is required to cover a broad range of infections. In this study, the effectiveness of novel monovalent and bivalent vaccines targeting EV71 C4a and CVA16 was investigated for their ability to prevent viral infections in neonatal human scavenger receptor class B member 2 (hSCARB2) transgenic mice. As hSCARB2 serves as a key viral receptor for EV71, these transgenic mice are susceptible to EV71 strains and facilitate viral binding, internalization, and uncoating processes. Antisera prepared by vaccine immunization were transferred to 2-day-old hSCARB2 transgenic mice, which were then infected with EV71 C4a or CVA16 virus. The antisera generated by each monovalent or bivalent vaccine effectively protected against EV71 C4a and CVA16 infections. The examination of tissue damage and viral contents in various organs indicated that both monovalent and bivalent antisera reduced EV71 C4a viral load in the brainstem, and no significant tissue damage was observed. During CVA16 infection, the monovalent and bivalent antisera significantly reduced viral contents in both the brainstem and muscles. These results suggest that passive immunity by monovalent and bivalent antisera can effectively protect against EV71 C4a and CVA16 infections. Thus, the development of a bivalent vaccine that can provide broad protection against both CV and EV infections may be a promising strategy in preventing HFMD.